The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor.
The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor.
复制标题
大麻素 delta-9-四氢大麻酚介导巨噬细胞对 RANTES/CCL5 趋化性的抑制：与 CB2 受体的连接。
DOI：
10.1007/s11481-007-9077-z
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Cabral,GuyA
中科院分区：
文献类型：
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作者：
Raborn,ErinnS;Marciano-Cabral,Francine;Buckley,NancyE;Martin,BillyR;Cabral,GuyA
小鼠腹腔巨噬细胞对RANTES/CCL 5的趋化反应在用δ-9-四氢大麻酚（THC）（大麻中的主要精神活性成分）预处理后显著抑制。当使用完全大麻素激动剂CP 55940时，也获得了对这种趋化因子定向的迁移反应的显著抑制。CB 2受体选择性配体O-2137对趋化性有强抑制作用，而CB 1受体选择性配体ACEA的作用最小。THC介导的抑制作用可被CB 2受体特异性拮抗剂SR 144528逆转，但不能被CB 1受体特异性拮抗剂SR 141716 A逆转。此外，THC处理对CB 2基因敲除小鼠腹腔巨噬细胞的趋化反应影响极小。总的来说，这些结果表明，大麻素通过CB 2受体的反式失活迁移反应RANTES/CCL 5。此外，结果表明，CB 2受体可能是一个网络的G蛋白偶联受体信号转导系统，包括趋化因子受体，协调行动，以调节巨噬细胞迁移的组成部分。
The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2receptor-specific antagonist SR144528 but not by the CB1receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2knockout mice. Collectively, these results suggest that cannabinoids act through the CB2receptor to transdeactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB2receptor may be a constituent element of a network of G protein-coupled receptor signal transductional systems, inclusive of chemokine receptors, that act coordinately to modulate macrophage migration.